This proposed R01 is a 5-year longitudinal bio-psycho-social integrative study of inner-city Hispanic adolescents, designed as a proof-of-concept of the neglected role of the neuromodulator BDNF (brain derived neurotrophic factor) in decision making (DM) and HIV-Transmission Risk Behaviors (TRBs). In addition to promising preliminary research findings, the impetus for this proposal is Hispanic seroprevalence in Florida, which is nearly twice the national rate. Long a primary U.S. epicenter, the latest available data shows that Florida's HIV epidemic is unexpectedly grim, ranking 3rd in cumulative AIDS cases, 2nd in cumulative pediatric cases. Because of heightened risk-taking, adolescents are considered among the high-risk HIV subgroups. Moreover, among 34 states in 2007, Florida ranked 2nd (behind New York) in the number of adolescents (13 to 19 years) living with HIV/AIDS, with the highest concentration in S. Florida's Miami-Dade and Broward counties, the sites of this proposal. This highlights the urgency for enhancing current understanding of risk and vulnerability factors in these minority subpopulations, particularly neurobiological factors that have been largely neglected in prior work and rarely examined in ethnic minority adolescents. The proposed study tests a theory-grounded- decision making model among Hispanic adolescents, which emphasizes the neuromodulator BDNF, extending its evaluation from alcohol/drug use to sexual risk behavior, in a framework that hypothesizes that disturbances are likely to: a) alter cognitive process;b) link to complex behaviors such as decision making and adaptation;and c) be highly relevant to problems in maintaining psychological well-being, particularly under stressful situations. The study also aims to explore the interaction of family/environment with adolescents'neurobiochemical factors in affecting HIV-TRBs given its pivotal role during adolescent brain development, and DM. With the support of local Health Departments, we propose to recruit 500 Hispanic adolescents (13-16 years), with follow-up over two years (3 time points) to examine the inter-relationships of biological and neuropsychological factors, and life experiences on HIV-TRBs, and to capture transition to later developmental stages. The proposed project is a transdisciplinary collaboration that will contribute new bio-behavioral knowledge to target neural mechanisms for which clinical solutions already exist. Treatments are currently available that may ameliorate suboptimal neurochemical levels (e.g., recombinant BDNF). In addition, because BDNF is implicated in both affective and cognitive dimensions of decision making, the proposed study also offers an innovative strategy for the highly sought-ever goal of integrating neurobiology into behavioral interventions among these susceptible populations.